Effect of mitochondrial dysfunction and oxidative stress on endogenous levels of coenzyme Q ₁₀ in human cells

Little is known about the regulation of endogenous CoQ ₁₀ levels in response to mitochondrial dysfunction or oxidative stress although exogenous CoQ ₁₀ has been extensively used in humans. In this study, we first demonstrated that acute treatment of antimycin A, an inhibitor of mitochondrial complex III, and the absence of mitochondrial DNA suppressed CoQ ₁₀ levels in human 143B cells. Because these two conditions also enhanced formation of reactive oxygen species (ROS), we further investigated whether oxidative stress or mitochondrial dysfunction primarily contributed to the decrease of CoQ ₁₀ levels. Results showed that H ₂O ₂ augmented CoQ ₁₀ levels, but carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP), a chemical uncoupler, decreased CoQ ₁₀ levels in 143B cells. However, H ₂O ₂ and FCCP both increased mRNA levels of multiple COQ genes for biosynthesis of CoQ ₁₀. Our findings suggest that ROS induced CoQ ₁₀ biosynthesis, whereas mitochondrial energy deficiency caused secondary suppression of CoQ ₁₀ levels possibly due to impaired import of COQ proteins into mitochondria.